Inflammation affects many individuals and is an underlying condition in a variety of diseases generally, inflammation is a body's defensive response to harmful stimuli used by animals to protect damaged areas and assist healing processes. As is known, pathogens, irritants, or damaged cells can trigger the inflammatory response leading to both acute and chronic forms of inflammation. Acute inflammation is generally defined as the body's initial response to harmful stimuli which involves increasing the movement of plasma and leukocytes to the injured area. Chronic inflammation is generally defined as the body's prolonged response to damaged tissue that leads to increased blood flow to and swelling of tissues over longer periods of time.
Despite the contribution of inflammation to healing, a variety of conditions including allergic reactions, atherosclerosis and rheumatoid arthritis can result from the cascade of biochemical events involved in the inflammation process. For example, inflammation can result from exposure to allergens in which a sensitized immune system will initiate antibody production in response to foreign objects. In this case, inflammatory mediators, such as histamine, are released leading to itching, swelling and mucous production. In other examples, atherosclerosis results from chronic inflammation in the walls of arteries leading to plaque formation and arterial narrowing. Rheumatoid arthritis involves an inflammatory response that attacks the synovial joints of an individual leading to pain and disfigurement.
Five types of allergic reactions have been identified. These include: allergy (immediate, Type I), cytotoxic and antibody-dependent (Type II), immune complex mediated (Type III), delayed-type hypersensitivity, cell-mediated immune memory response and antibody-independent (Type IV), and autoimmune disease and receptor mediated (Type V) Immediate or Type I allergic reactions are largely attributed to IgE antibodies, although IgG antibodies can participate in and modulate allergic reactions The allergy is generally caused by the activation of a subpopulation of immune cells, the mast cells and basophils when antigen reacts with IgE antibody receptors on the cell's surface the chemical mediators initiate the allergic reaction by acting on adjacent immune, epithelial, endothelial and smooth muscle cells and promote, in a longer term, the influx of other inflammatory and immune cells (neutrophils, eosinophils, monocytes, lymphocytes) into tissue. This influx of inflammatory cells predisposes the patient to recurrent and sometimes delayed, or prolonged allergic or hypersensitivity reactions. A distinction between immediate and delayed allergic reactions and delayed, chronic immune injury can also be made. The Type 1 allergic reactions are defined according to the location where they occur. Asthmatic reactions occur in the lungs, rhinitis in the nose, conjunctivitis, iritis and uveitis in the eyes, urticaria (hives), atopic dermatitis and eczema in the outer skin dermis, angioedema occurs in dermis subcutaneous tissue, mucosa and submucosal tissues. Systemic allergic reactions in the circulation and in the gastrointestinal system and are often life threatening. Anaphylactic shock, the most severe form of allergy, is a medical emergency. It is often severe and sometimes can provoke a fatal systemic reaction in a susceptible individual upon exposure to a specific antigen (as wasp venom or penicillin) after previous sensitization. Anaphylactic shock is characterized by respiratory symptoms, fainting, itching, urticaria, swelling of the throat or other mucous membranes and a sudden decline in blood pressure. Symptoms of anaphylactic shock include dizziness, loss of consciousness, labored breathing, swelling of the tongue, blueness of the skin, bronchospasm, low blood pressure, and death.
Asthma can be defined clinically as a condition of intermittent, reversible airways obstruction, and manifests itself as several clinical entities: allergic asthma, bronchial asthma, exercise induced asthma, chemical induced asthma, and static asthma. Asthma can be divided into two types. Extrinsic asthma is generally triggered by external agents such as allergens (dust mites, pollen, stings, drugs, or foods), and is commonly diagnosed in early life. Intrinsic asthma, which generally develops later in life, can be triggered by congested and inflamed tissues, infection, endogenous catecholamines (e.g. adrenaline), drugs (e.g. aspirin), stress or exertion. Inflammation can also be triggered by a number of stimuli including heat and chemical burns, exposure to toxins, damaged tissue due to environmental exposure (e.g. frostbite), infections including bacteria, viruses, and parasites, physical injury, immune reactions including allergic reactions and autoimmune conditions, exposure to radiation, as well as the presence of foreign bodies such as splinters or dirt.
Symptoms of inflammation include redness of the affected area, swollen and/or sore joints, stiffness of joints and in some cases even loss of joint function. Fever, chills and fatigue may also be side effects of an inflammatory response in the individual. In addition to these side effects, a number of diseases can result from chronic inflammation including asthma, hay fever, tendonitis, bursitis, arthritis, diabetes, heart disease, atherosclerosis, atopic dermatitis (eczema), contact dermatitis, psoriasis, irritable bowel syndrome, Crohn's disease, colitis, ileitis, gastritis, diverticulitis, ulcerative colitis hepatitis, nephritis, lupus erythematosus, Alzheimer's disease, Parkinson's disease and even cancer.
Treating inflammation typically involves the use of pharmaceuticals such as non-steroidal and steroidal anti-inflammatory drugs, Non-steroidal anti-inflammatory drugs (NSAIDs) can include over the counter medications such as aspirin, ibuprofen or naproxen. NSAIDs generally work by blocking the cyclooxygenase enzymes responsible for the production of prostaglandins; a group of lipid compounds that promote inflammation. Other pharmaceuticals include methotrexate, sulfasalazine, anti-TNF medications, cyclophosphamide and mycophenolate.
Steroidal treatments often involve the use of corticosteroids that act on the immune system to block the production of substances that trigger allergic and inflammatory reactions. Like NSAIDs, corticosteroids inhibit prostaglandin production thereby reducing the normal inflammatory response in the individual.
Immune-selective anti-inflammatory derivatives (NSAIDs) are another class of anti-inflammatory compounds. Generally, (NSAIDs) are a class of peptides that alter the activation of immune cells (leukocytes) responsible for the inflammatory response.
Natural approaches can also be used to treat inflammation. Herbs such as willow bark, meadowsweet, ginger, ginseng, and licorice, have been shown to exhibit anti-inflammatory properties. Omega-3 fatty acids have also been shown to induce an anti-inflammatory response in addition to vitamins Bi 2, C and E and the minerals copper and zinc.
Nutraceuticals such as probiotics, which are defined as healthy microorganisms living in the intestinal tract of mammals, and prebiotics, the non-digestible food ingredients that stimulate the growth of healthy bacteria, have also shown anti-inflammatory properties. Symbiotics, which combine prebiotics with probiotics, can be used for treating, alleviating and reducing the symptoms associated with inflammation.
The disadvantages of the above treatments are the adverse effects that may be associated with direct use and/or combinational risk Both gastrointestinal and renal effects, which can lead to hypertension, are the most common side effects of NSAIDs use. Cardiovascular risk is possible as well as the potential to adversely affect the fetus during pregnancy. Since prostaglandins protect the stomach and assist in blood clotting, NSAIDs can lead to stomach ulcers and promote bleeding.
Corticosteroids impede the function of white blood cells which keep the immune system functioning properly. Over time, use of corticosteroids can affect the function of the adrenal glands responsible for the natural production of corticosteroids. They can also increase the risk of high blood pressure and bone diseases such as osteoporosis. Upset stomach and vomiting are common in addition to sleep problems and indigestion. The lowering of an individual's resistance to infection is a risk and prolonged use can lead to organ failure.
The use of prebiotics, probiotics or their combination (symbiotics) run the risk of having their therapeutic effect altered when added to food products. Different preparation methods may impart different health effects. As such, their quality can be difficult to guarantee. They may also cause gas and/or bloating due to the activity of the microorganisms.
Although the use of vitamins and minerals is generally regarded as safe, excess usage can lead to adverse side effects. Vitamin C can cause nausea and diarrhea when recommended allowances are exceeded while vitamin E can lead to weakness and fatigue. Vitamin B12 may induce diarrhea and insomnia in certain individuals.
Another natural source of anti-inflammatory compounds is various bee products. More specifically, the use of some bee products is known to offer an anti-inflammatory response when used as a nutraceutical or applied topically. Such bee products include beeswax, propolis, royal jelly, honey, bee bread and bee pollen.
By way of background and as is known, beeswax is a compound used by bees to construct honeycombs, and is composed of free fatty acids (12-14%), free primary fatty alcohols (1%), linear wax monoesters and hydroxymonoesters (35-45%), complex wax esters (15-27%>, and odd numbered straight chain hydrocarbons (12-16%) with predominant chain lengths of C27-C33. The incorporation of pollen and propolis give beeswax its distinct yellow colour. Propolis is a resinous mixture collected by bees from botanical sources and is used as a sealant for repairing the beehive, Royal jelly is the bee secretion used to feed the larvae destined to become queen bees, which as a food source is used to trigger the development of queen morphology Honey is a food source for bees made using the nectar from flowers. Bee bread is pollen packed into granules using honey and nectar and is used as a method to store pollen and bee pollen is the main energy source for the bees.
The above bee products are understood to have a variety of health benefits and their incorporation into both food products and nutraceuticals are widespread and in high demand. For example, various bee products have been used as complimentary medicines to treat a variety of disorders. In addition to treating inflammation, bee products have been used to allegedly provide protection against cold and flu viruses, to enhance energy and libido, reduce stress and depression, regulate hormones, suppress an unhealthy appetite, moderate body weight, rebuild bones and tissue, treat impotence and stomach ulcers, and as a dietary supplement to fight against cancer, high cholesterol and cardiac conditions.
Specifically, bee pollen is used as a general prophylactic and is believed to provide protection against cold and flu viruses, enhance energy, libido, stamina and mood, reduce stress and depression, regulate hormones, suppress cravings and an unhealthy appetite, moderate body weight, rebuild bones, tissue and muscle, treat anemia, asthma, allergic conditions, impotence, bleeding stomach ulcers, altitude sickness, and as a dietary supplement has been used for cancer, high cholesterol, cardiac conditions [1,2], and treatment of the prostate [3]. The German Federal Board of Health has recognized bee pollen as a medicine [2], Propolis, due to its antimicrobial and immunomodulatory properties, is used by natural health practitioners to relieve inflammations, viral diseases, ulcers, skin disorders, treating the common cold, wounds and burns, sore throats and dental plaque [1,3]. Royal jelly is proposed to have benefits in treating weak bones, endocrine system disorders, arthritis, asthma, impotence and infertility, Parkinson's disease, retarded growth, bacterial infections, and other disorders [1]. The use of royal jelly for health purposes is not widely reported [3]. Even honey, a common food source, is a natural energy booster, immune system builder and an aid in many common ailments, such as cuts and burns, and sooth sore throats. It is an emollient and contains anti-microbial properties [1].
Bee pollen, which is a mixture of flower pollen, honeybee digestive juices, and nectar, is a rich source of protein, carbohydrate, vitamins, and minerals. It contains a variety of secondary plant products such as flavenoids, carotenoids, and terpenes [4]. Concerning its use in allergies, bee pollen induces oral desensitization in patients suffering from pollen allergy [5], and several recent animal studies have shown that bee pollen inhibits allergic reactions. Specifically, a phenolic extract of bee pollen inhibited paw edema, IgE (immunoglobulin E) and IgG1 (immunoglobulin G1) ovalbumin-specific production, leukocyte migration to the lungs (bronchoalveolar lavage; (BAL)), and eosinophil peroxidise (EPO) activity in lungs of ovalbumin-sensitized mice. Daily oral administration of bee pollen to mice significantly reduced the IgE specific antigen elicited cutaneous mast cell activation, and in vitro reductions were seen in mast cell degranulated and tumor necrosis factor production consequent to inhibition of IgE binding to receptors (FcERI) could read Fc.di-elect cons.RI [6].
Higher aliphatic primary alcohols purified from beeswax (Apis mellifera) have cytoprotective effects and exhibit moderate anti-ulcer effects in animals and humans [7]. Triacontanol is the most abundant component this mixture, called D-002, followed by octacosanol and hexacosanol, while tetracosanol, dotriacontanol, and tetratriacontanol are present in lower concentrations [8]. Literature citations on beeswax and allergy generally indicate a propensity to cause allergies, rather than prevent them [9,10], and similar findings are reported with propolis [11, 12].
It is also known that some bee products such as bee pollen can induce an allergic reaction in certain individuals, particularly those afflicted by ragweed allergies. The purification of bee products often involves a number of extraction steps to obtain the isolated product. These steps may involve a plurality of organic solvents, saponification and grounding, long periods of time for suspensions to form, separating the bee products from a complex mixture of other botanical compounds and mixing with a number of additives to increase bioactivity.
In addition to the above, a review of the patent prior art confirms that the use of “bee products” has been extensively studied in relation to the various health benefits that may result from the use of such products.
For example, previous work involving bee products include U.S. Pat. No. 7,141,611 by Gamble et al. who extract aliphatic alcohols from beeswax and bee pollen to use as an anti-inflammatory agent in pharmaceuticals, foodstuffs and dietary supplements. U.S. Pat. No. 6,482,442 to Dato discloses a mixture comprising honey and olive oil along with beeswax, propolis, royal jelly, honey and pollen to treat a variety of ailments including inflammation; US Pat. No. 7,351,739 to Ho et al., U.S. Pat. No. 6,342,255 to De Gregorio, 2010/0034905 to Sembrano, U.S. Pat. No. 6,649,178 to Mohammadi et al., and U.S. Pat. No. 6,579,543 to McClung disclose the use of pollen and/or bee pollen to treat inflammation; U.S. Pat. No. 7,763,282 to Corvi Mora et al., and 2010/0074964 to Glavas disclose the use of propolis to treat inflammation; US Patent Publication No. 2005/0048128 to Miyata et al. discloses the use of royal jelly to treat inflammation; and, U.S. Pat. No. 2,494,907 mentions the ability of beeswax bloom to contain applied germ killing sulfa drugs used to prevent the spread of American foulbrood.
While there is increasing commercial interest in natural products to treat inflammation and other related disorders and conditions, there remain problems and issues with existing products which limit their overall usefulness and safety.
It is an object of the present invention to obviate or mitigate some or all of the above noted disadvantages.